Intermittent fasting has gained global popularity for its potential health benefits, although its impact on somatic stem cells and tissue biology remains elusive. Here, we report that commonly used intermittent fasting regimens inhibit hair follicle regeneration by selectively inducing apoptosis in activated hair follicle stem cells (HFSCs). This effect is independent of calorie reduction, circadian rhythm alterations, or the mTORC1 cellular nutrient-sensing mechanism. Instead, fasting activates crosstalk between adrenal glands and dermal adipocytes in the skin, triggering the rapid release of free fatty acids into the niche, which in turn disrupts the normal metabolism of HFSCs and elevates their cellular reactive oxygen species levels, causing oxidative damage and apoptosis. A randomized clinical trial (NCT05800730) indicates that intermittent fasting inhibits human hair growth. Our study uncovers an inhibitory effect of intermittent fasting on tissue regeneration and identifies interorgan communication that eliminates activated HFSCs and halts tissue regeneration during periods of unstable nutrient supply.

中文翻译：

---

间歇性禁食触发器官间通讯以抑制毛囊再生


间歇性禁食因其潜在的健康益处而在全球范围内广受欢迎，尽管它对体细胞干细胞和组织生物学的影响仍然难以捉摸。在这里，我们报道了常用的间歇性禁食方案通过选择性诱导活化的毛囊干细胞 （HFSC） 凋亡来抑制毛囊再生。这种效果与卡路里减少、昼夜节律改变或 mTORC1 细胞营养感应机制无关。相反，禁食会激活皮肤中肾上腺和真皮脂肪细胞之间的串扰，触发游离脂肪酸快速释放到生态位中，进而破坏 HFSC 的正常代谢并提高其细胞活性氧水平，导致氧化损伤和细胞凋亡。一项随机临床试验 （NCT05800730） 表明，间歇性禁食会抑制人类头发的生长。我们的研究揭示了间歇性禁食对组织再生的抑制作用，并确定了在营养供应不稳定期间消除激活的 HFSC 并停止组织再生的器官间通讯。